IL-1\u03b2 increases asporin expression via the NF-\u03baB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration

Shengjie Wang,Jiwei Tian,He Liang,Changwei Li,Zhongyi Sun,Kai Huang,Chao Liu,Peng Yan

doi:10.1038/s41598-017-04384-3

Abstract

Disc degeneration (DD) is a multifaceted chronic process that alters the structure and function of intervertebral discs. The pathophysiology of degeneration is not completely understood, but the consensus is that changes in genes encoding extracellular matrix (ECM) proteins in the disc are the leading factors contributing to DD. Asporin is an ECM protein that has been shown to be increased in degenerated intervertebral discs, but little is known about how asporin is regulated during DD. In exploring the intricate mechanism, we confirmed that asporin was abundantly increased in patients’ degenerated nucleus pulposus. Consistently, the increased asporin expression with degeneration was also proved by rabbit intervertebral disc degeneration (IDD) model. Mechanistically, IL-1β upregulated asporin expression by activating the p65 pathway in human nucleus pulposus cells. Furthermore, p65 mediated asporin expression by binding to −41/−31 bp on asporin promoter. Functionally, asporin was the intermediator of IL-1β-inhibited aggrecan and collagen Π expression and played a negative role in TGF-β-induced aggrecan and collagen Π formation in human nucleus pulposus cells. Therefore, identifying asporin as a negative regulator of aggrecan and collagen Π and elucidating its induction mechanisms in human nucleus pulposus cells provides new insight for asporin induction during IDD.

Highlights

Disc degeneration (DD) is a multifaceted chronic process that can lead to herniation, radiculopathy, myelopathy, spinal stenosis, and degenerative spondylolisthesis, resulting in acute or chronic pain that alters the structure and function of the intervertebral discs and can lead to painful conditions[1]
The genes encoding extracellular matrix (ECM) proteins expressed in the nucleus pulposus and annulus fibrosus of the disc, such as type Π collagen, type IX collagen, aggrecan, and cartilage intermediate layer protein (CILP), have been shown to be risk factors for disc degeneration[6,7,8,9]
Increased asporin has been reported during disc degeneration, the intricate underlying mechanism by which asporin becomes involved in the pathogenesis of disc degeneration remains largely unknown

Summary

Introduction

Disc degeneration (DD) is a multifaceted chronic process that can lead to herniation, radiculopathy, myelopathy, spinal stenosis, and degenerative spondylolisthesis, resulting in acute or chronic pain that alters the structure and function of the intervertebral discs and can lead to painful conditions[1]. It is a common and serious problem worldwide that affects 40% of individuals younger than 30 years old and more than 90% of those older than 50 years old[2]. Our findings uncovered a vital detrimental role of asporin in promoting disc degeneration and delineated a previously unknown intrinsic regulatory mechanism

Methods

Results

Conclusion